Long-term effects of adolescent stress on neophobic behaviors in zebra finches are modulated by social context when in adulthood

Funding was provided by a BBSRC Research Fellowship to KAS and a University of St Andrews postgraduate scholarship to MGE.Experiencing stress during adolescence can increase neophobic behaviors in adulthood, but most tests have been conducted in the absence of conspecifics. Conspecifics can modulate responses to stressors, for example by acting as ‘social buffers’ to attenuate the aversive appraisal of stressors. Here, we investigate the long-term effects of adolescent stress on the behavioral responses to novel stimuli (a mild stressor) across social contexts in an affiliative passerine bird, the zebra finch. During early (days 40–60) or late (days 65–85) adolescence the birds (n = 66) were dosed with either saline or the hormone corticosterone (CORT). CORT was given in order to mimic a physiological stress response and saline was given as a control. In adulthood, the birds' behavioral responses to a novel environment were recorded in both the presence and absence of conspecifics. An acute CORT response was also quantified in adolescence and adulthood. Our findings show clear evidence of social context mediating any long-term effects of adolescent stress. In the presence of familiar conspecifics no treatment effects were detected. Individually, birds dosed with CORT in early adolescence were slower to enter a novel environment, spent more time perching in the same novel environment, and, if female, engaged in more risk assessment. Birds dosed in late adolescence were unaffected. No treatment effects were detected on CORT, but adolescents had a higher CORT concentration than adults. Our results are the first to suggest that familiar conspecifics in adulthood can buffer the long-term effects of stress that occurred during early adolescence.Publisher PDFPeer reviewe

Group housing during adolescence has long-term effects on the adult stress response in female, but not male, zebra finches (Taeniopygia guttata)

Funding was provided by a BBSRC David Phillips Research Fellowship to KAS and a University of St Andrews postgraduate scholarship to MGE.Adolescent social interactions can have long-term effects on physiological responses to stressors in later-life. A larger adolescent group size can result in higher stressor-induced secretion of glucocorticoids in adulthood. The effect may be due to a socially-mediated modulation of gonadal hormones, e.g. testosterone. However, group size (number of animals) has been conflated with social density (space per animal). Therefore it is hard to determine the mechanisms through which adolescent group size can affect the stress response. The current study aimed to tease apart the effects of group size and social density during adolescence on the physiological stress response and gonadal hormone levels in adulthood. Adolescent zebra finches were housed in groups varying in size (2 vs. 5 birds per cage) and density (0.03m3 vs. 0.06m3 per bird) during early adolescence (day 40-60). Density was only manipulated in birds raised in groups of five. Glucocorticoid concentration secreted in response to a standard capture and restraint stressor was quantified in adolescence (day 55±1) and adulthood (day 100+). Basal gonadal hormones concentrations (male testosterone, female estradiol) were also quantified in adulthood. Female birds housed in larger groups, independent of social density, secreted a higher glucocorticoid concentration 45 mins into restraint regardless of age, and had higher peak glucocorticoid concentration in adulthood. Adult gonadal hormone concentrations were not affected by group size or density. Our results suggest that group size, not density, is a social condition that influences the development of the endocrine response to stressors in female zebra finches, and that these effects persist into adulthood. The findings have clear relevance to the social housing conditions necessary for optimal welfare in captive animals, but also elucidate the role of social rearing conditions in the emergence of responses to stressors that may persist across the lifespan and affect fitness of animals in wild populations.Publisher PDFPeer reviewe

Social experience during adolescence in female rats increases 50 kHz ultrasonic vocalizations in adulthood, without affecting anxiety-like behavior

Funding was provided by a University of St Andrews postgraduate studentship to MGE.Adolescents are highly motivated to engage in social interactions, and researchers have hypothesized that positive social relationships during adolescence can have long term, beneficial effects on stress reactivity and mental well‐being. Studies of laboratory rodents provide the opportunity to investigate the relationship between early social experiences and later behavioral and physiological responses to stressors. In this study, female Lister‐hooded rats (N = 12 per group) were either (a) provided with short, daily encounters (10 min/day) with a novel partner during mid‐adolescence (postnatal day 34–45; “social experience,” SE, subjects) or (b) underwent the same protocol with a familiar cagemate during mid‐adolescence (“control experience,” CE, subjects), or (c) were left undisturbed in the home cage (non‐handled “control,” C, subjects). When tested in adulthood, the groups did not differ in behavioral responses to novel environments (elevated plus maze, open field, and light‐dark box) or in behavioral and physiological (urinary corticosterone) responses to novel social partners. However, SE females emitted significantly more 50 kHz ultrasonic vocalizations than control subjects both before and after social separation from a familiar social partner, which is consistent with previous findings in male rats. Thus, enhanced adolescent social experience appears to have long‐term effects on vocal communication and could potentially modulate adult social relationships.PostprintPeer reviewe

Temperature response measurements from eucalypts give insight into the impact of Australian isoprene emissions on air quality in 2050

Predicting future air quality in Australian cities dominated by eucalypt emissions requires an understanding of their emission potentials in a warmer climate. Here we measure the temperature response in isoprene emissions from saplings of four different Eucalyptus species grown under current and future average summertime temperature conditions. The future conditions represent a 2050 climate under Representative Concentration Pathway 8.5, with average daytime temperatures of 294.5 K. Ramping the temperature from 293 to 328 K resulted in these eucalypts emitting isoprene at temperatures 4–9 K higher than the default maximum emission temperature in the Model of Emissions of Gases and Aerosols from Nature (MEGAN). New basal emission rate measurements were obtained at the standard conditions of 303 K leaf temperature and 1000 µmol m−2 s−1 photosynthetically active radiation and converted into landscape emission factors. We applied the eucalypt temperature responses and emission factors to Australian trees within MEGAN and ran the CSIRO Chemical Transport Model for three summertime campaigns in Australia. Compared to the default model, the new temperature responses resulted in less isoprene emission in the morning and more during hot afternoons, improving the statistical fit of modelled to observed ambient isoprene. Compared to current conditions, an additional 2 ppb of isoprene is predicted in 2050, causing hourly increases up to 21 ppb of ozone and 24-hourly increases of 0.4 µg m−3 of aerosol in Sydney. A 550 ppm CO2 atmosphere in 2050 mitigates these peak Sydney ozone mixing ratios by 4 ppb. Nevertheless, these forecasted increases in ozone are up to one-fifth of the hourly Australian air quality limit, suggesting that anthropogenic NOx should be further reduced to maintain healthy air quality in future

The Association of Dietary Intake of Purine-Rich Vegetables, Sugar-Sweetened Beverages and Dairy with Plasma Urate, in a Cross-Sectional Study

Peer reviewedPublisher PD

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course